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基本情報
登録情報 | ![]() | |||||||||
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タイトル | phospho-STING binding to adaptor protein complex-1 | |||||||||
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![]() | STING / innate immunity / TGN / AP-1 / IMMUNE SYSTEM | |||||||||
機能・相同性 | ![]() basolateral protein secretion / AP-1 adaptor complex / endosome to melanosome transport / Lysosome Vesicle Biogenesis / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / platelet dense granule organization / Glycosphingolipid transport / regulation of receptor internalization / melanosome assembly ...basolateral protein secretion / AP-1 adaptor complex / endosome to melanosome transport / Lysosome Vesicle Biogenesis / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / platelet dense granule organization / Glycosphingolipid transport / regulation of receptor internalization / melanosome assembly / STING complex / Intra-Golgi traffic / regulation of Arp2/3 complex-mediated actin nucleation / STAT6-mediated induction of chemokines / Golgi Associated Vesicle Biogenesis / Synthesis of PIPs at the Golgi membrane / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / clathrin adaptor activity / cyclic-di-GMP binding / STING mediated induction of host immune responses / MHC class II antigen presentation / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / Nef Mediated CD4 Down-regulation / dendritic spine organization / IRF3-mediated induction of type I IFN / proton channel activity / cGAS/STING signaling pathway / determination of left/right symmetry / long-term synaptic depression / clathrin-coated vesicle / reticulophagy / pattern recognition receptor signaling pathway / COPI-dependent Golgi-to-ER retrograde traffic / clathrin binding / Lysosome Vesicle Biogenesis / cytoplasmic pattern recognition receptor signaling pathway / Golgi Associated Vesicle Biogenesis / cellular response to exogenous dsRNA / cell leading edge / Synthesis of PIPs at the plasma membrane / protein complex oligomerization / positive regulation of macroautophagy / autophagosome membrane / autophagosome assembly / intracellular copper ion homeostasis / positive regulation of type I interferon production / protein targeting / cellular response to interferon-beta / COPI-mediated anterograde transport / vesicle-mediated transport / clathrin-coated pit / signaling adaptor activity / positive regulation of defense response to virus by host / antiviral innate immune response / Neutrophil degranulation / endoplasmic reticulum-Golgi intermediate compartment membrane / MHC class II antigen presentation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / activation of innate immune response / cytoplasmic vesicle membrane / Regulation of innate immune responses to cytosolic DNA / autophagosome / positive regulation of interferon-beta production / positive regulation of DNA-binding transcription factor activity / secretory granule membrane / Nef mediated downregulation of MHC class I complex cell surface expression / sarcomere / small monomeric GTPase / trans-Golgi network membrane / kidney development / intracellular protein transport / trans-Golgi network / cellular response to virus / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / synaptic vesicle / peroxisome / presynapse / heart development / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / early endosome / neuron projection / postsynaptic density / endosome / ciliary basal body / cilium / protein domain specific binding / Golgi membrane / lysosomal membrane / innate immune response / focal adhesion / GTPase activity / intracellular membrane-bounded organelle / synapse / ubiquitin protein ligase binding 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.34 Å | |||||||||
![]() | Xu P / Ablasser A | |||||||||
資金援助 | European Union, 1件
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![]() | ![]() タイトル: Clathrin-associated AP-1 controls termination of STING signalling. 著者: Ying Liu / Pengbiao Xu / Sophie Rivara / Chong Liu / Jonathan Ricci / Xuefeng Ren / James H Hurley / Andrea Ablasser / ![]() ![]() 要旨: Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate ...Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate immunity during infection, cancer and immunotherapy. Precise regulation of STING is essential to ensure balanced immune responses and prevent detrimental autoinflammation. After activation, STING, a transmembrane protein, traffics from the endoplasmic reticulum to the Golgi, where its phosphorylation by the protein kinase TBK1 enables signal transduction. The mechanism that ends STING signalling at the Golgi remains unknown. Here we show that adaptor protein complex 1 (AP-1) controls the termination of STING-dependent immune activation. We find that AP-1 sorts phosphorylated STING into clathrin-coated transport vesicles for delivery to the endolysosomal system, where STING is degraded. We identify a highly conserved dileucine motif in the cytosolic C-terminal tail (CTT) of STING that, together with TBK1-dependent CTT phosphorylation, dictates the AP-1 engagement of STING. A cryo-electron microscopy structure of AP-1 in complex with phosphorylated STING explains the enhanced recognition of TBK1-activated STING. We show that suppression of AP-1 exacerbates STING-induced immune responses. Our results reveal a structural mechanism of negative regulation of STING and establish that the initiation of signalling is inextricably associated with its termination to enable transient activation of immunity. | |||||||||
履歴 |
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 51.9 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 22.6 KB 22.6 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.8 KB | 表示 | ![]() |
画像 | ![]() | 119.2 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
その他 | ![]() ![]() | 95.5 MB 95.5 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7r4hMC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.9 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_14312_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_14312_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : phospho-STING binding to adaptor protein complex-1
全体 | 名称: phospho-STING binding to adaptor protein complex-1 |
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要素 |
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-超分子 #1: phospho-STING binding to adaptor protein complex-1
超分子 | 名称: phospho-STING binding to adaptor protein complex-1 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: ![]() |
-分子 #1: AP-1 complex subunit beta-1
分子 | 名称: AP-1 complex subunit beta-1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 66.008422 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MTDSKYFTTT KKGEIFELKA ELNSDKKEKK KEAVKKVIAS MTVGKDVSAL FPDVVNCMQT DNLELKKLVY LYLMNYAKSQ PDMAIMAVN TFVKDCEDPN PLIRALAVRT MGCIRVDKIT EYLCEPLRKC LKDEDPYVRK TAAVCVAKLH DINAQLVEDQ G FLDTLKDL ...文字列: MTDSKYFTTT KKGEIFELKA ELNSDKKEKK KEAVKKVIAS MTVGKDVSAL FPDVVNCMQT DNLELKKLVY LYLMNYAKSQ PDMAIMAVN TFVKDCEDPN PLIRALAVRT MGCIRVDKIT EYLCEPLRKC LKDEDPYVRK TAAVCVAKLH DINAQLVEDQ G FLDTLKDL ISDSNPMVVA NAVAALSEIA ESHPSSNLLD LNPQSINKLL TALNECTEWG QIFILDCLAN YMPKDDREAQ SI CERVTPR LSHANSAVVL SAVKVLMKFM EMLSKDLDYY GTLLKKLAPP LVTLLSAEPE LQYVALRNIN LIVQKRPEIL KHE MKVFFV KYNDPIYVKL EKLDIMIRLA SQANIAQVLA ELREYATEVD VDFVRKAVRA IGRCAIKVEQ SAERCVSTLL DLIQ TKVNY VVQEAIVVIK DIFRKYPNKY ESVIATLCEN LDSLDEPEAR AAMIWIVGEY AERIDNADEL LESFLEGFHD KSTQV QLQL LTAIVKLFLK KPTETQELVQ QVLSLATQDS DNPDLRDRGY IYWRLLSTDP VAAKEVVLAE KPLISEETDL IEPTLL DEL ICYIGTLASV YHKPPSAFVE G UniProtKB: AP-1 complex subunit beta-1 |
-分子 #2: ADP-ribosylation factor 1
分子 | 名称: ADP-ribosylation factor 1 / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 18.9366 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: EMRILMVGLD AAGKTTILYK LKLGEIVTTI PTIGFNVETV EYKNISFTVW DVGGLDKIRP LWRHYFQNTQ GLIFVVDSND RERVNEARE ELMRMLAEDE LRDAVLLVFA NKQDLPNAMN AAEITDKLGL HSLRHRNWYI QATCATSGDG LYEGLDWLSN Q LRNQK UniProtKB: ADP-ribosylation factor 1 |
-分子 #3: AP-1 complex subunit gamma-1
分子 | 名称: AP-1 complex subunit gamma-1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 67.399242 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MPAPIRLREL IRTIRTARTQ AEEREMIQKE CAAIRSSFRE EDNTYRCRNV AKLLYMHMLG YPAHFGQLEC LKLIASQKFT DKRIGYLGA MLLLDERQDV HLLMTNCIKN DLNHSTQFVQ GLALCTLGCM GSSEMCRDLA GEVEKLLKTS NSYLRKKAAL C AVHVIRKV ...文字列: MPAPIRLREL IRTIRTARTQ AEEREMIQKE CAAIRSSFRE EDNTYRCRNV AKLLYMHMLG YPAHFGQLEC LKLIASQKFT DKRIGYLGA MLLLDERQDV HLLMTNCIKN DLNHSTQFVQ GLALCTLGCM GSSEMCRDLA GEVEKLLKTS NSYLRKKAAL C AVHVIRKV PELMEMFLPA TKNLLNEKNH GVLHTSVVLL TEMCERSPDM LAHFRKLVPQ LVRILKNLIM SGYSPEHDVS GI SDPFLQV RILRLLRILG RNDDDSSEAM NDILAQVATN TETSKNVGNA ILYETVLTIM DIKSESGLRV LAINILGRFL LNN DKNIRY VALTSLLKTV QTDHNAVQRH RSTIVDCLKD LDVSIKRRAM ELSFALVNGN NIRGMMKELL YFLDSCEPEF KADC ASGIF LAAEKYAPSK RWHIDTIMRV LTTAGSYVRD DAVPNLIQLI TNSVEMHAYT VQRLYKAILG DYSQQPLVQV AAWCI GEYG DLLVSGQCEE EEPIQVTEDE VLDILESVLI SNMSTSVTRG YALTAIMKLS TRFTCTVNRI KKVVSIYGSS IDVELQ QRA VEYNALFKKY DHMRSALLER MPVMEKVTTN GP UniProtKB: AP-1 complex subunit gamma-1 |
-分子 #4: Stimulator of interferon genes protein
分子 | 名称: Stimulator of interferon genes protein / タイプ: protein_or_peptide / ID: 4 / 詳細: phospho-STING tail / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 1.065068 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QEPELLI(SEP)G UniProtKB: Stimulator of interferon genes protein |
-分子 #5: AP-1 complex subunit mu-1
分子 | 名称: AP-1 complex subunit mu-1 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 48.60673 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSASAVYVLD LKGKVLICRN YRGDVDMSEV EHFMPILMEK EEEGMLSPIL AHGGVRFMWI KHNNLYLVAT SKKNACVSLV FSFLYKVVQ VFSEYFKELE EESIRDNFVI IYELLDELMD FGYPQTTDSK ILQEYITQEG HKLETGAPRP PATVTNAVSW R SEGIKYRK ...文字列: MSASAVYVLD LKGKVLICRN YRGDVDMSEV EHFMPILMEK EEEGMLSPIL AHGGVRFMWI KHNNLYLVAT SKKNACVSLV FSFLYKVVQ VFSEYFKELE EESIRDNFVI IYELLDELMD FGYPQTTDSK ILQEYITQEG HKLETGAPRP PATVTNAVSW R SEGIKYRK NEVFLDVIEA VNLLVSANGN VLRSEIVGSI KMRVFLSGMP ELRLGLNDKV LFDNTGRGKS KSVELEDVKF HQ CVRLSRF ENDRTISFIP PDGEFELMSY RLNTHVKPLI WIESVIEKHS HSRIEYMVKA KSQFKRRSTA NNVEIHIPVP NDA DSPKFK TTVGSVKWVP ENSEIVWSVK SFPGGKEYLM RAHFGLPSVE AEDKEGKPPI SVKFEIPYFT TSGIQVRYLK IIEK SGYQA LPWVRYITQN GDYQLRTQ UniProtKB: AP-1 complex subunit mu-1 |
-分子 #6: AP-1 complex subunit sigma-3
分子 | 名称: AP-1 complex subunit sigma-3 / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 18.321338 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MIHFILLFSR QGKLRLQKWY ITLPDKERKK ITREIVQIIL SRGHRTSSFV DWKELKLVYK RYASLYFCCA IENQDNELLT LEIVHRYVE LLDKYFGNVC ELDIIFNFEK AYFILDEFII GGEIQETSKK IAVKAIEDSD MLQEVSTVCQ TMGER UniProtKB: AP-1 complex subunit sigma-3 |
-分子 #7: GUANOSINE-5'-TRIPHOSPHATE
分子 | 名称: GUANOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 7 / コピー数: 2 / 式: GTP |
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分子量 | 理論値: 523.18 Da |
Chemical component information | ![]() ChemComp-GTP: |
-分子 #8: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 8 / コピー数: 2 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.8 mg/mL | |||||||||||||||
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緩衝液 | pH: 7.4 構成要素:
詳細: PBS buffer | |||||||||||||||
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 30 sec. | |||||||||||||||
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |